2,1-Benzothiazine - (quinolin/thiophen)yl hydrazone frameworks as new monoamine oxidase inhibitory agents; synthesis, in vitro and in silico investigation

• Published in: RSC advances 2023-01, Vol.13 (3), p.1701-1710
• Main Authors: Javid, Noman, Jalil, Saquib, Munir, Rubina, Zia-Ur-Rehman, Muhammad, Sahar, Amna, Arshad, Sara, Iqbal, Jamshed
• Format: Article
• Language: English
• Subjects: Chemistry; Hydrazones; Inhibitors; Molecular docking; Neurological diseases; NMR; Nuclear magnetic resonance; Oxidase; Synthesis
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d2ra07045f

Two series of new 2,1-benzothiazine derivatives have been synthesized by condensation of 4-hydrazono-1-methyl-3,4-dihydro-1 -benzo[ ][1,2]thiazine 2,2-dioxide (5) with 2-chloroquinoline-3-carbaldehydes and acetylthiophenes to acquire new heteroaryl ethylidenes 7(a-f) and 9(a-k) in excellent yields. After characterization by FTIR, H NMR, C NMR and elemental analyses, the newly synthesized analogues were investigated against monoamine oxidase enzymes (MAO A and MAO B). The titled compounds exhibited activity in the lower micromolar range among which 9e was the most potent compound against MAO A with IC of 1.04 ± 0.01 μM whereas 9h proved to be the most potent derivative against MAO B with an IC value of 1.03 ± 0.17 μM. Furthermore, results were further endorsed by molecular docking studies to determine the interaction between the potent compounds and the enzyme active site. These newly synthesized compounds represent promising hits for the development of safer and potent lead molecules for therapeutic use against depression and other neurological diseases.